Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2

Silvestri,; Barrowdale, V.; Dmulligan, A. M. c.; Author, Demail; Neuhausen,; eEmail Author, S. L.; Fox,; fEmail Author, S.; Karlan,; gEmail Author, B. Y.; Mitchell, G. h.; Author, Iemail; James, P. h.; Author, Iemail; Thull,; jEmail Author, D. L.; Zorn,; jEmail Author, K. K.; Carter,; kEmail Author, N. J.; Nathanson,; lEmail Author, K. L.; Domchek,; lEmail Author, S. M.; Rebbeck,; mEmail Author, T. R.; Ramus,; nEmail Author, S. J.; Nussbaum,; oEmail Author, R. L.; Olopade,; pEmail Author, O. I.; Rantala,; qEmail Author, J.; Yoon,; S. -Y. r.,; Author, Semail; Caligo,; tEmail Author, M. A.; Spugnesi,; tEmail Author, L.; Bojesen,; uEmail Author, A.; Pedersen,; vEmail Author, I. S.; Thomassen,; wEmail Author, M.; Jensen,; xEmail Author, U. B.; Toland,; yEmail Author, A. E.; Senter,; zEmail Author, L.; Andrulis, I. L. d.; Aa,; Author, Abemail; Glendon,; aaEmail Author, G.; Hulick,; acEmail Author, P. J.; Imyanitov,; adEmail Author, E. N.; Greene,; aeEmail Author, M. H.; Mai,; aeEmail Author, P. L.; Singer,; afEmail Author, C. F.; Rappaport-Fuerhauser,; afEmail Author, C.; Kramer,; agEmail Author, G.; Vijai,; ahEmail Author, J.; Offit,; ahEmail Author, K.; Robson,; aiEmail Author, M.; Lincoln,; ahEmail Author, A.; Jacobs,; ahEmail Author, L.; Machackova,; ajEmail Author, E.; Foretova,; akEmail Author, L.; Navratilova,; ajEmail Author, M.; Vasickova,; ajEmail Author, P.; Couch,; F. J., Al; Author, Amemail; Hallberg,; amEmail Author, E.; Ruddy,; anEmail Author, K. J.; Sharma,; aoEmail Author, P.; Kim,; apEmail Author, S. -W.; Teixeira,; M. R., Aq; Author, Aremail; Pinto,; aqEmail Author, P.; Montagna,; asEmail Author, M.; Matricardi,; asEmail Author, L.; Arason,; atEmail Author, A.; Johannsson,; auEmail Author, O. T.; Barkardottir,; atEmail Author, R. B.; Jakubowska,; avEmail Author, A.; Lubinski,; avEmail Author, J.; Izquierdo,; awEmail Author, A.; Pujana,; axEmail Author, M. A.; Balmaña,; ayEmail Author, J.; Diez,; azEmail Author, O.; Ivady,; baEmail Author, G.; Papp,; bbEmail Author, J.; Olah,; bbEmail Author, E.; Kwong,; Bc, A.; Author, Bdemail; Nevanlinna,; beEmail Author, H.; Aittomäki,; bfEmail Author, K.; Segura, Perez; bgEmail Author, P.; Caldes,; bhEmail Author, T.; Maerken, Van; biEmail Author, T.; Poppe,; biEmail Author, B.; Claes,; biEmail Author, K. B. M.; Isaacs,; bjEmail Author, C.; Elan,; bkEmail Author, C.; Lasset,; Bl, C.; Author, Bmemail; Stoppa-Lyonnet,; Bk, D.; Author, Bnemail; Barjhoux,; boEmail Author, L.; Belotti,; bkEmail Author, M.; Meindl,; bpEmail Author, A.; Gehrig,; bqEmail Author, A.; Sutter,; brEmail Author, C.; Engel,; bsEmail Author, C.; Niederacher,; btEmail Author, D.; Steinemann,; buEmail Author, D.; Hahnen,; bvEmail Author, E.; Kast,; bwEmail Author, K.; Arnold,; bxEmail Author, N.; Varon-Mateeva,; byEmail Author, R.; Wand,; bzEmail Author, D.; Godwin,; caEmail Author, A. K.; Evans,; cbEmail Author, D. G.; Frost,; bEmail Author, D.; Perkins,; bEmail Author, J.; Adlard,; ccEmail Author, J.; Izatt,; cdEmail Author, L.; Platte,; ceEmail Author, R.; Eeles,; cfEmail Author, R.; Ellis,; bEmail Author, S.; Hamann,; cfEmail Author, U.; Garber,; cgEmail Author, J.; Fostira,; chEmail Author, F.; Fountzilas,; ciEmail Author, G.; Pasini,; Cj, B.; Author, Ckemail; Giannini,; aEmail Author, G.; Rizzolo,; aEmail Author, P.; Russo,; clEmail Author, A.; Cortesi,; cmEmail Author, L.; Papi, Laura; cnEmail Author, L.; Varesco,; coEmail Author, L.; Palli,; cpEmail Author, D.; Zanna,; cpEmail Author, I.; Savarese,; cqEmail Author, A.; Radice,; crEmail Author, P.; Manoukian,; csEmail Author, S.; Peissel,; csEmail Author, B.; Barile,; ctEmail Author, M.; Bonanni,; ctEmail Author, B.; Viel,; cuEmail Author, A.; Pensotti,; Cv, V.; Author, Cwemail; Tommasi,; cxEmail Author, S.; Peterlongo,; cvEmail Author, P.; Weitzel,; cyEmail Author, J. N.; Osorio,; Cz, A.; Author, Daemail; Benitez,; Da, J.; Db,; Author, Dcemail; Mcguffog,; bEmail Author, L.; Healey,; ddEmail Author, S.; Gerdes,; deEmail Author, A. -M.; Ejlertsen,; dfEmail Author, B.; Hansen,; dgEmail Author, T. V. O.; Steele,; eEmail Author, L.; Ding,; eEmail Author, Y. C.; Tung,; dhEmail Author, N.; Janavicius,; diEmail Author, R.; Goldgar,; djEmail Author, D. E.; Buys,; dkEmail Author, S. S.; Daly,; dlEmail Author, M. B.; Bane,; dmEmail Author, A.; Terry,; dnEmail Author, M. B.; John,; doEmail Author, E. M.; Southey,; dpEmail Author, M.; Easton,; bEmail Author, D. F.; Chenevix-Trench,; ddEmail Author, G.; Antoniou,; bEmail Author, A. C.; Ottini,; Papi, L

doi:10.1186/s13058-016-0671-y

BACKGROUND: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). METHODS: We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10(-12)). CONCLUSIONS: On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.

Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2 / Silvestri, V. Barrowdale, DMulligan, A.M.c,dEmail Author, Neuhausen, S.L.eEmail Author, Fox, S.fEmail Author, Karlan, B.Y.gEmail Author, Mitchell, G.h,iEmail Author, James, P.h,iEmail Author, Thull, D.L.jEmail Author, Zorn, K.K.jEmail Author, Carter, N.J.kEmail Author, Nathanson, K.L.lEmail Author, Domchek, S.M.lEmail Author, Rebbeck, T.R.mEmail Author, Ramus, S.J.nEmail Author, Nussbaum, R.L.oEmail Author, Olopade, O.I.pEmail Author, Rantala, J.qEmail Author, Yoon, S.-Y.r,sEmail Author, Caligo, M.A.tEmail Author, Spugnesi, L.tEmail Author, Bojesen, A.uEmail Author, Pedersen, I.S.vEmail Author, Thomassen, M.wEmail Author, Jensen, U.B.xEmail Author, Toland, A.E.yEmail Author, Senter, L.zEmail Author, Andrulis, I.L.d,aa,abEmail Author, Glendon, G.aaEmail Author, Hulick, P.J.acEmail Author, Imyanitov, E.N.adEmail Author, Greene, M.H.aeEmail Author, Mai, P.L.aeEmail Author, Singer, C.F.afEmail Author, Rappaport-Fuerhauser, C.afEmail Author, Kramer, G.agEmail Author, Vijai, J.ahEmail Author, Offit, K.ahEmail Author, Robson, M.aiEmail Author, Lincoln, A.ahEmail Author, Jacobs, L.ahEmail Author, Machackova, E.ajEmail Author, Foretova, L.akEmail Author, Navratilova, M.ajEmail Author, Vasickova, P.ajEmail Author, Couch, F.J.al,amEmail Author, Hallberg, E.amEmail Author, Ruddy, K.J.anEmail Author, Sharma, P.aoEmail Author, Kim, S.-W.apEmail Author, Teixeira, M.R.aq,arEmail Author, Pinto, P.aqEmail Author, Montagna, M.asEmail Author, Matricardi, L.asEmail Author, Arason, A.atEmail Author, Johannsson, O.T.auEmail Author, Barkardottir, R.B.atEmail Author, Jakubowska, A.avEmail Author, Lubinski, J.avEmail Author, Izquierdo, A.awEmail Author, Pujana, M.A.axEmail Author, Balmaña, J.ayEmail Author, Diez, O.azEmail Author, Ivady, G.baEmail Author, Papp, J.bbEmail Author, Olah, E.bbEmail Author, Kwong, A.bc,bdEmail Author, Nevanlinna, H.beEmail Author, Aittomäki, K.bfEmail Author, Perez Segura, P.bgEmail Author, Caldes, T.bhEmail Author, Van Maerken, T.biEmail Author, Poppe, B.biEmail Author, Claes, K.B.M.biEmail Author, Isaacs, C.bjEmail Author, Elan, C.bkEmail Author, Lasset, C.bl,bmEmail Author, Stoppa-Lyonnet, D.bk,bnEmail Author, Barjhoux, L.boEmail Author, Belotti, M.bkEmail Author, Meindl, A.bpEmail Author, Gehrig, A.bqEmail Author, Sutter, C.brEmail Author, Engel, C.bsEmail Author, Niederacher, D.btEmail Author, Steinemann, D.buEmail Author, Hahnen, E.bvEmail Author, Kast, K.bwEmail Author, Arnold, N.bxEmail Author, Varon-Mateeva, R.byEmail Author, Wand, D.bzEmail Author, Godwin, A.K.caEmail Author, Evans, D.G.cbEmail Author, Frost, D.bEmail Author, Perkins, J.bEmail Author, Adlard, J.ccEmail Author, Izatt, L.cdEmail Author, Platte, R.ceEmail Author, Eeles, R.cfEmail Author, Ellis, S.bEmail Author, Hamann, U.cfEmail Author, Garber, J.cgEmail Author, Fostira, F.chEmail Author, Fountzilas, G.ciEmail Author, Pasini, B.cj,ckEmail Author, Giannini, G.aEmail Author, Rizzolo, P.aEmail Author, Russo, A.clEmail Author, Cortesi, L.cmEmail Author, Papi, L.cnEmail Author, Varesco, L.coEmail Author, Palli, D.cpEmail Author, Zanna, I.cpEmail Author, Savarese, A.cqEmail Author, Radice, P.crEmail Author, Manoukian, S.csEmail Author, Peissel, B.csEmail Author, Barile, M.ctEmail Author, Bonanni, B.ctEmail Author, Viel, A.cuEmail Author, Pensotti, V.cv,cwEmail Author, Tommasi, S.cxEmail Author, Peterlongo, P.cvEmail Author, Weitzel, J.N.cyEmail Author, Osorio, A.cz,daEmail Author, Benitez, J.da,db,dcEmail Author, McGuffog, L.bEmail Author, Healey, S.ddEmail Author, Gerdes, A.-M.deEmail Author, Ejlertsen, B.dfEmail Author, Hansen, T.V.O.dgEmail Author, Steele, L.eEmail Author, Ding, Y.C.eEmail Author, Tung, N.dhEmail Author, Janavicius, R.diEmail Author, Goldgar, D.E.djEmail Author, Buys, S.S.dkEmail Author, Daly, M.B.dlEmail Author, Bane, A.dmEmail Author, Terry, M.B.dnEmail Author, John, E.M.doEmail Author, Southey, M.dpEmail Author, Easton, D.F.bEmail Author, Chenevix-Trench, G.ddEmail Author, Antoniou, A.C.bEmail Author, Ottini, Papi L. - In: BREAST CANCER RESEARCH. - ISSN 1465-5411. - STAMPA. - 18:(2016), pp. 15-27. [10.1186/s13058-016-0671-y]